Researchers Are Getting Closer to Learning How to Treat and Prevent Long COVID

Three years into the COVID-19 pandemic, with millions of people around the world suffering from long-term complications of the virus, there is still no proven way to treat or prevent Long COVID—besides not getting infected in the first place.

Recently, however, there’s been reason for cautious optimism. Researchers have found promising (though preliminary) signs that certain drugs may reduce the risk of developing Long COVID, and possibly even ease symptoms among people who are already sick.

The latest hopeful news relates to metformin, an accessible and affordable drug that’s been U.S. Food and Drug Administration (FDA)-approved to treat Type 2 diabetes since the 1990s. Metformin, which belongs to a class of drugs called biguanides, is taken as a liquid or pill and works by controlling the amount of sugar in the blood. It also decreases inflammation in the body.

In a study that was posted online in March but has not yet been peer-reviewed, researchers tracked a group of 564 overweight or obese U.S. adults who started a two-week course of metformin when they had acute COVID-19. People who took metformin had a 42% lower chance of being diagnosed with Long COVID over the following 10 months, compared to those who took a placebo when they first got sick with COVID-19. (The study also tracked the effects of drugs ivermectin and fluvoxamine, but neither showed a benefit against Long COVID.)

Metformin appeared to be even more effective when used early. Among people who took it within four days of developing symptoms, the risk of Long COVID dropped by more than 60%. In total, about 6% of people who took metformin went on to be diagnosed with Long COVID, compared to more than 10% of the people who took a placebo.

Other studies have shown that metformin can stop the SARS-CoV-2 virus from replicating, which may help prevent both severe disease and long-term complications, explains principal investigator Dr. Carolyn Bramante, an assistant professor at the University of Minnesota Medical School. Metformin seems to work against the virus by blocking a protein in human cells that the virus uses to copy itself, and by disrupting the inflammatory response caused by the virus, she says.

Bramante says she was pleasantly surprised by how well metformin seemed to prevent Long COVID, especially when taken right away, although more research is required to confirm the findings. “It’s probably in every pharmacy in the world,” Bramante says. Someone could likely “get metformin within a day of knowing they have COVID.”

In the future, Bramante says, researchers should also study whether metformin can treat existing Long COVID symptoms. Some experts believe Long COVID is caused by remnants of the virus lingering in the body. If that’s true, Bramante says, metformin’s antiviral properties might help clear it from the body.

Other recent studies have also suggested that Paxlovid, an antiviral drug used to prevent severe COVID-19 among high-risk patients, may help prevent Long COVID in a similar way. One study, which was posted online in late 2022 but had not been peer-reviewed, found that people who took Paxlovid within five days of testing positive for COVID-19 had a 26% lower risk of developing Long COVID, compared to an untreated control group. (Ensitrelvir, another antiviral drug that is authorized in Japan but not the U.S., may also reduce the risk of developing Long COVID when taken shortly after testing positive, its manufacturer announced in February.)

Some researchers are also studying whether Paxlovid can treat Long COVID symptoms—an important question, since there is still no proven cure for Long COVID.

Read More: People Are Far Less Likely to Get Long COVID After Omicron, Study Finds

Long COVID is difficult to treat, at least in part because the disease takes many forms. One person might have debilitating fatigue and brain fog while another could have gastrointestinal issues or nervous-system dysfunction. Instead of trying to find a single drug that can treat all of Long COVID’s 200-plus potential symptoms, some research teams are zeroing in on specific symptoms, or groups of them, in hopes of finding targeted therapies.

Some tools used to treat people with myalgic encephalomyelitis/chronic fatigue syndrome, a post-viral condition that shares key symptoms with Long COVID (including extreme fatigue and crashes after exertion), may also be effective for people with post-COVID complications, according to an article published in Nature Reviews Microbiology in January. These tools include an energy-rationing strategy known as pacing, the anti-inflammatory drug low-dose naltrexone, and beta blockers to slow heart rate and lower blood pressure. Antihistamines have also been shown in small studies to reduce some Long COVID symptoms, including fatigue, brain fog, and an inability to exercise, as have blood-thinning drugs.

Dr. Eric Topol, founder of the Scripps Research Translational Institute and co-author of the recent review, says he’s also encouraged by preliminary data on stimulation of the vagus nerve, which helps control unconscious actions like breathing and heart rate, to ease certain symptoms.

Multiple research teams are also studying transcranial direct current stimulation (tDCS) as a potential treatment. Researchers have already studied whether tDCS devices—which administer low-intensity electrical currents to the scalp to stimulate the brain—can improve cognition, mental health, and chronic pain. Consumers can buy a variety of tDCS devices to use at home, though many have not been cleared by the FDA.

In one small study that was posted online in September 2022 but had not been peer-reviewed, researchers found that, after eight tDCS sessions, people with Long COVID reported reductions in physical fatigue and depression, though mental fatigue and overall quality of life scores didn’t improve.

Clinical neurologist and study co-author Dr. Jordi Matias-Guiu says he’s planning a longer follow-up study, with patients receiving treatments for three weeks, to see if that leads to better results. “This should be confirmed in other clinical trials, but the findings are encouraging,” he says. “This is a technique that could be administered at home, and this is a non-invasive technique with minimal [side effects].”

The list of potential treatments is growing, but the field needs larger, more coordinated research projects, Topol says; at the moment, most findings are coming from small studies that need to be peer-reviewed, expanded, and duplicated. RECOVER, the U.S. National Institutes of Health’s $1 billion Long COVID research project, has begun designing trials of potential treatments, but they haven’t turned into therapies yet.

The lack of proven treatments is disappointing, Topol says, but he considers the recent findings about metformin’s potential to prevent Long COVID “very good news.”

Topol agrees that more studies on metformin are needed—but he says he believes that the early findings are promising enough, and the drug is safe and cheap enough, that he would personally take it now if he got sick with COVID-19. “I don’t want to get Long COVID,” Topol says.